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The angiotensin AT₄ receptor subtype as a target for the treatment of memory dysfunction associated with Alzheimer's disease

Departments of Psychology, Veterinary and Comparative Anatomy, Pharmacology, and Physiology, and Program in Neuroscience, Washington State University, P.O. Box 644820, Pullman, WA 99164-4820, USA, wrightjw{at}wsu.edu

Joseph W Harding

Departments of Psychology, Veterinary and Comparative Anatomy, Pharmacology, and Physiology, and Program in Neuroscience, Washington State University, P.O. Box 644820, Pullman, WA 99164-4820, USA

Over recent years antihypertensive drugs, particularly angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), have been reported to have beneficial effects upon cognitive impairment. Such findings suggest that pharmacological manipulation of angiotensin ligands may be of clinical importance in slowing or halting the cognitive deterioration seen in vascular dementia and Alzheimer's disease.The mechanism(s) underlying these improvements in cognitive function remains unclear; however, important leads are emerging. The angiotensin AT ₄ receptor subtype, discovered by our laboratory in 1992, influences several important behaviours and physiologies, including learning and memory, and may play a role in this cognitive improvement.This review initially describes the therapeutic drugs approved by the Federal Drug Administration and new approaches presently being developed to treat Alzheimer's disease-induced cognitive impairment. Next, the biologically-active angiotensin ligands and their respective receptor subtypes are discussed, followed by the roles of angiotensin II, angiotensin IV, ACE inhibitors and ARBs in cognitive function.We conclude with a working hypothesis concerning the importance of the AT₄ receptor subtype as a new potential drug target for the treatment of Alzheimer's disease-associated memory loss.

Key Words: ACE inhibitors • Alzheimer's disease • angiotensin II • angiotensin IV • angiotensin receptor blockers • AT1 receptor • AT4 receptor • dementia • renin-angiotensin system

Journal of Renin-Angiotensin-Aldosterone System, Vol. 9, No. 4, 226-237 (2008)
DOI: 10.1177/1470320308099084


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